This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Compared to placebo, treatment with Citicoline for 90 days following a traumatic brain injury improves recovery of cognitive deficits as measured by a core neuropsychological battery at 90 days post-injury. Nearly 1300 subjects with an acute complicated (i.e. with evidence of injury on head CT) mild (Glasgow Coma Scale (GCS) score 13-15), moderate (GCS 9-12) or severe (GCS 3-8) TBI will be recruited from eight clinical sites composing the TBI Clinical Trials (TBI-CT) Network that includes the Virginia Commonwealth University Medical Center, University of Maryland, Temple University, University of Tennessee, University of Alabama Birmingham, University of Texas Southwestern Medical Center, University of Pittsburgh, and University of Washington. Participants who have met all enrollment criteria will be randomly assigned to receive 1000 mg bid Citicoline or placebo bid under double-blind conditions. The first dose will be given within 24 hours of injury and treatment will continue for 90 days. Functional outcome will be assessed at 30-, 90- and 180-days post-injury. The primary outcome consists of a set of measures that will be analyzed as a composite measure using a global statistic at 90 days. This composite measure is comprised of the following core battery: Extended Glasgow Outcome Scale (GOS-E), Controlled Oral Word Association Test (COWAT), Processing Speed Index (PSI), Trail Making Test parts A, Trail Making Test part B, Stroop Test, California Verbal Learning Test (CVLT), and Digit Span and analyzed using the global statistic. Secondary outcomes will include survival, toxicity, and rate of recovery. There is some evidence to suggest that a form of a gene called Apo-E gene may be associated with recovery after a TBI. It is likely that other genes may also influence the amount of recovery and healing after a head injury. One part of the COBRIT study is to determine whether the Apo-E gene is associated with recovery and with response to Citicoline. Another part is to store frozen blood and CSF samples for later testing as new information becomes available.